Treating Zoster-Associated Pain and Postherpetic Neuralgia

Each year an estimated 1 million Americans experience herpes zoster, or shingles.¹ In most cases, the rash clears in 2 to 4 weeks without complications, but in as many as 20% of cases, damage to the nerve fibers causes postherpetic neuralgia (PHN).² Although herpes zoster is most common after age 50, it can affect anyone who has had chickenpox, particularly if they are immunocompromised.

Both the acute pain of shingles (zoster-associated pain, or ZAP) and PHN drive many patients to seek medical care. Although a primary care physician is often the first point of contact, patients may see a dermatologist because of the rash. Both primary care physicians and dermatologists may refer more difficult-to-treat cases to a neurologist or other pain specialist.

“Most of the time, if [PHN] is pretty severe, I may refer to a neurologist at that point,” said David Hecker, MD, co-owner of Hecker Dermatology Group PA, in Pompano Beach, FL. “But if they come to me and they have a skin lesion and pain associated with that, then I basically treat both.”

Dr Hecker, who says he treats about five new cases of shingles per month, was one of 12 physicians—dermatologists as well as family physicians and neurologists—interviewed recently about the treatment of ZAP and PHN. All of the physicians treated at least one patient with ZAP or PHN monthly. One of them, Stephen K. Tyring, MD, PhD, a dermatologist and clinical professor at the University of Texas Health Science Center in Houston, said he sees as many as 30 patients with ZAP or PHN a month. The age of patients typically treated by the physicians ranged from their 40s to their 90s, with most in their 60s and 70s.

Almost all of the experts interviewed said they prescribe some type of pharmaceutical for patients with PHN or ZAP. Most preferred prescription treatments vs over-the-counter (OTC) ones, with a few indicating that they rely entirely on prescription medications. The treatment varied depending on various factors, including the stage of infection (active shingles vs PHN), patient and physician preference, and patient age and comorbidities.

Antivirals. The respondents generally agreed that they would use an antiviral initially for acute shingles, but beyond that, there is probably no benefit.

“The antivirals should be given acutely during the shingles episode,” said Alan David Kaye, MD, PhD, a professor in the departments of anesthesiology, toxicology, and neurosciences at Louisiana State University School of Medicine in Shreveport. “There is no role for antivirals for PHN.”

“By the time they come to me, they’re good at least 4 weeks out,” says Annet Falchook, MD, of Boca Raton Neurologic Associates in Boca Raton, FL.  “So, antiviral really shouldn’t work anymore.”

Topical analgesics. While antivirals were used during the earliest stages of herpes zoster, topical analgesics were more likely to be used to relieve pain after the blisters have crusted over or healed. Of the topicals prescribed or recommended by the physicians, the most common was lidocaine (either 4% OTC or 5% prescription cream), although some preferred other options, such as lidocaine patches and capsaicin, including an 8% capsaicin medication that must be applied by a health care professional.

“I may use a lidocaine patch,” said Steven P. Cohen, MD, chief of pain medicine at Johns Hopkins University School of Medicine in Baltimore, MD. “There are some lidocaine patches that are available [OTC], which seem to work comparably to prescription medications.”

“I haven’t used [lidocaine patches] before or topical lidocaine, just the capsaicin,” said Evan Schlam, MD, of Evan Schlam Dermatology in Plantation and voluntary clinical professor of dermatology, University of Miami Miller School of Medicine in Florida. “It’s made from red pepper and it’s the main ingredient. It causes an icy hot kind of feel.”

OTC lidocaine was often chosen for cost, particularly if there were issues with insurance coverage for the prescription lidocaine. An OTC lidocaine cream or gel “might be appropriate particularly for a person who doesn’t have good drug coverage and needs something that’s inexpensive,” said Jessica Robinson-Papp, MD, associate professor of neurology at the Icahn School of Medicine at Mountain Sinai in New York City, NY.

Anticonvulsants and antidepressants. Of the drugs used to treat ZAP and PHN, the experts’ top choices were anticonvulsants, particularly gabapentin and pregablin, both of which have FDA approval for PHN, followed by antidepressants, including duloxetine and venlafaxine.

“Probably the most common medications that we use for postherpetic neuralgia are the gabapentinoids,” said Dr Robinson-Papp. “They tend to have not too many drug interactions, which is useful. And they tend to be fairly well-tolerated. So, that’s usually my first line.”

“I would only do gabapentin first,” said Michael Burke, MD, a family medicine specialist in Delray Beach, FL. “And then if it really gets into a longer course of pain, then I’m reaching for amitriptyline.”

The full prescribing information for gabapentin states the dose can be titrated up as needed to a dose of 1800 mg per day. For pregabalin the maximum daily dose is 600 mg, divided into two or three doses per day.

As with any drug, the respondents said they used lower doses depending on the patient’s age and comorbidities.

Dr Kaye said he minimizes risks of side effects by using an extended-release form of gabapentin “that provides efficacy with the least amount of side effects such as sedation.” He says, unfortunately, many prescribers are unfamiliar with the extended-release formulation and underprescribe gabapentin to reduce the incidence of sedation or only give it at night, which does not provide 24-hour coverage.

Nonsteroidal anti-inflammatory drugs (NSAIDs). Although patients may turn to OTC NSAIDs to relieve both ZAP and PHN, some respondents said they would not recommend or prescribe NSAIDs due to lack of efficacy for neuropathic pain and the risks associated with NSAIDs in older patients.

“I shy away from long-term NSAIDs, particularly in elderly patients in general,” said Dr Falchook. “But specific to PHN and ZAP, I don’t find [there is] a place for it. In general, nerve pain doesn’t really respond to nonsteroidal anti-inflammatories because the nerve itself is injured.”

Some physicians who indicated they would not recommend or prescribe NSAIDS added that these drugs may be appropriate in certain circumstances. “I use them because that’s what the patient is usually taking before they come in to the clinic,” said Dr Tyring. “So, if they’re taking [NSAIDs], I don’t tell them to stop because they will still take them if they have pain. I just try to decrease their use by adding in the gabapentin or pregabalin.”

Other drugs. Other drugs mentioned as part of treatment for ZAP or PHN included prednisone for an acute rash and acetaminophen and opioid analgesics for pain.

Satisfaction with current therapies for ZAP and PHN varied among the respondents, with most reporting moderate satisfaction for at least some patients and others reporting general dissatisfaction among patients.

“I’d say they do good for some patients. And for other patients, they get no benefit,” said Justin Bailey, MD, of Family Medicine Residency of Idaho in Boise.  “So, I think it really depends on that patient,” he added.

“In general, patients are very, very, very unsatisfied with their choices for PHN or ZAP,” said Dr Kaye.

Treatment concerns ranged from efficacy of treatments overall to the side effects of specific treatments that might limit or prevent their use in certain populations.

“I would say just that there are a lot of options that ufortunately are not always efficacious,” said Dane Pohlman, DO, an interventional pain management physician in Coral Springs, FL. “And I think that’s the concern. There’s not always a homerun.”

“Since there is no perfect treatment, I’d say that the lack of efficacious treatment or at least medical treatment is always a concern,” said Dr Tyring. “It doesn’t always respond to medicine except powerful narcotics, which I tried not to prescribe.”

More specific concerns cited include risk of arrhythmias and adhesion issues with lidocaine patches; the inability to use topicals on herpes zoster affecting the eye; and nervous system depression by antineuropathic medications, which can cause cognitive and psychomotor effects.

As the shingles vaccine is more widely used, cases of shingles are decreasing. The respondents were divided as to whether that translates to fewer cases or decreased severity of PHN.

“I haven’t seen any data showing this yet if there really is less of a chance of PHN, but I have a hunch that there is,” said Dr Hecker. “This is based on my own clinical experience with patients. I think in the future, PHN will be much lower than herpes zoster.”

“If you are vaccinated and you still happen to get zoster, the likelihood of PHN and significant pain is lower,” said Dr Robinson-Papp.

“So, essentially, without zoster vaccine actually, we did see an increase in patients getting zoster afterwards,” said Marc H. Feinberg, MD, of South Florida Neurology Associates in Boca Raton and Delray Beach, FL. “So, we did see that. Whether there was a lower incidence of PHN, I’m not sure.”

Regardless of whether the vaccine will eventually reduce the incidence or severity of ZAP and PHN, the respondents agreed better treatments were needed. If a new drug candidate had superior efficacy on pain suppression compared with 5% lidocaine and was safe for long-term use, most said they would consider it as a first choice for treatment, perhaps in combination with or even as a replacement for others for other treatments.

“These patients are suffering. Neuropathic pain is the worst type of pain,” said Dr Feinberg. “Anything we could do to alleviate the discomfort would be helpful. If we added a better topical agent that really worked, we would definitely use it, or at least give it a try.”

“If there was a topical that did seem to actually not just mask the pain but control it, I would probably just eliminate everything else and use that alone,” said Dr Falchook, adding the importance of avoiding medication interaction with polypharmacy.

Qualities the experts mentioned that would make a topical the first choice of treatment included greater efficacy and fewer side effects than oral treatment; nongreasy formulation applied no more than twice daily to improve compliance; ease of application, including easy-to-open packaging; and affordability/covered by insurance.

If the new drug candidate had efficacy in PHN the respondents said they might consider using it for other types of neuropathic pain and pruritus. “If a patient has pain of unknown etiology, I would say that I would prescribe it until way we can figure out the true cause of their pain,” said Dr Tyring.

“I think anything that’s causing a discomfort or pruritus [could] probably be useful,” said Dr Schlam.

Dermatologists often see and treat the herpes zoster cutaneous presentation, although ZAP is commonly treated by primary care physicians. Persistent pain due to PHN may require a consultation with or treatment by a neurologist. Physicians prescribe or recommend a wide range of treatments for ZAP and PHN, commonly beginning with antivirals and perhaps the use of NSAIDs or acetaminophen during the acute stage of infection. For persistent pain, they may progress to OTC and prescription topicals, anticonvulsants, and antidepressants and in some cases narcotic analgesics.

Most respondents gave the current treatments less-than-perfect scores and said they would welcome a new topical treatment that worked differently from lidocaine. Many said they would use that treatment along with or even in place of current treatments. Most said that is such a treatment were available it would likely have a role in the management of a range of conditions in addition to PHN, including pruritus and different forms of neuropathic pain.